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1
Dong, Xiaoguang, Guo Zhan Lum, Wenqi Hu, Rongjing Zhang, Ziyu Ren, Patrick R. Onck, and Metin Sitti. "Bioinspired cilia arrays with programmable nonreciprocal motion and metachronal coordination." Science Advances 6, no. 45 (November 2020): eabc9323. http://dx.doi.org/10.1126/sciadv.abc9323.
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Coordinated nonreciprocal dynamics in biological cilia is essential to many living systems, where the emergentmetachronal waves of cilia have been hypothesized to enhance net fluid flows at low Reynolds numbers (Re). Experimental investigation of this hypothesis is critical but remains challenging. Here, we report soft miniature devices with both ciliary nonreciprocal motion and metachronal coordination and use them to investigate the quantitative relationship between metachronal coordination and the induced fluid flow. We found that only antiplectic metachronal waves with specific wave vectors could enhance fluid flows compared with the synchronized case. These findings further enable various bioinspired cilia arrays with unique functionalities of pumping and mixing viscous synthetic and biological complex fluids at low Re. Our design method and developed soft miniature devices provide unprecedented opportunities for studying ciliary biomechanics and creating cilia-inspired wireless microfluidic pumping, object manipulation and lab- and organ-on-a-chip devices, mobile microrobots, and bioengineering systems.
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Sears, Patrick R., Kristin Thompson, Michael R. Knowles, and C. William Davis. "Human airway ciliary dynamics." American Journal of Physiology-Lung Cellular and Molecular Physiology 304, no. 3 (February 1, 2013): L170—L183. http://dx.doi.org/10.1152/ajplung.00105.2012.
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Airway cilia depend on precise changes in shape to transport the mucus gel overlying mucosal surfaces. The ciliary motion can be recorded in several planes using video microscopy. However, cilia are densely packed, and automated computerized systems are not available to convert these ciliary shape changes into forms that are useful for testing theoretical models of ciliary function. We developed a system for converting planar ciliary motions recorded by video microscopy into an empirical quantitative model, which is easy to use in validating mathematical models, or in examining ciliary function, e.g., in primary ciliary dyskinesia (PCD). The system we developed allows the manipulation of a model cilium superimposed over a video of beating cilia. Data were analyzed to determine shear angles and velocity vectors of points along the cilium. Extracted waveforms were used to construct a composite waveform, which could be used as a standard. Variability was measured as the mean difference in position of points on individual waveforms and the standard. The shapes analyzed were the end-recovery, end-effective, and fastest moving effective and recovery with mean (± SE) differences of 0.31(0.04), 0.25(0.06), 0.50(0.12), 0.50(0.10), μm, respectively. In contrast, the same measures for three different PCD waveforms had values far outside this range.
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Valentine, Megan, and Judith Van Houten. "Using Paramecium as a Model for Ciliopathies." Genes 12, no. 10 (September 24, 2021): 1493. http://dx.doi.org/10.3390/genes12101493.
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Paramecium has served as a model organism for the studies of many aspects of genetics and cell biology: non-Mendelian inheritance, genome duplication, genome rearrangements, and exocytosis, to name a few. However, the large number and patterning of cilia that cover its surface have inspired extraordinary ultrastructural work. Its swimming patterns inspired exquisite electrophysiological studies that led to a description of the bioelectric control of ciliary motion. A genetic dissection of swimming behavior moved the field toward the genes and gene products underlying ciliary function. With the advent of molecular technologies, it became clear that there was not only great conservation of ciliary structure but also of the genes coding for ciliary structure and function. It is this conservation and the legacy of past research that allow us to use Paramecium as a model for cilia and ciliary diseases called ciliopathies. However, there would be no compelling reason to study Paramecium as this model if there were no new insights into cilia and ciliopathies to be gained. In this review, we present studies that we believe will do this. For example, while the literature continues to state that immotile cilia are sensory and motile cilia are not, we will provide evidence that Paramecium cilia are clearly sensory. Other examples show that while a Paramecium protein is highly conserved it takes a different interacting partner or conducts a different ion than expected. Perhaps these exceptions will provoke new ideas about mammalian systems.
4
Vanaki, Shayan M., David Holmes, Pahala Gedara Jayathilake, and Richard Brown. "Three-Dimensional Numerical Analysis of Periciliary Liquid Layer: Ciliary Abnormalities in Respiratory Diseases." Applied Sciences 9, no. 19 (September 26, 2019): 4033. http://dx.doi.org/10.3390/app9194033.
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Human pulmonary epithelial cells are protected by two layers of fluid—the outer watery periciliary liquid layer (PCL) and the uppermost non-Newtonian mucus layer (ML). Aerosols and inhaled toxic particles are trapped by the ML which must then be removed swiftly to avoid adverse health implications. Epithelial cells are covered with cilia that beat rapidly within the PCL. Such ciliary motion drives the mucus transport. Although cilia can penetrate slightly inside the mucus to assist mucus movement, the motion of the underlying PCL layer within the airway surface liquid (ASL) is significant in mucus and pathogens transport. As such, a detailed parametric study of the influence of different abnormal cilia characteristics, such as low beating frequency, short length, abnormal beating pattern, reduced ciliary density, and epithelium patchiness due to missing cilia on the PCL transport, is carried out numerically. Such abnormalities are found in various chronic respiratory diseases. In addition, the shear stress at the epithelium is assessed due to the importance of shear stress on the epithelial function. Using the immersed boundary (IB) method combined with the finite-difference projection method, we found that the PCL, under standard healthy conditions, has net forward motion but that different diseased conditions decrease the forward motion of the PCL, as is expected based on clinical understanding.
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Sher Akbar, Noreen, and Z. H. Khan. "Heat transfer analysis of bi-viscous ciliary motion fluid." International Journal of Biomathematics 08, no. 02 (February 25, 2015): 1550026. http://dx.doi.org/10.1142/s1793524515500266.
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The impulsion system of cilia motion is deliberated by biviscosity fluid model. The problem of two-dimensional motion of biviscosity fluid privileged in a symmetric channel with ciliated walls is considered. The features of ciliary structures are resolute by the supremacy of viscous effects above inertial possessions by the long-wavelength and low Reynolds approximation. Closed-form solutions for the longitudinal pressure gradient, temperature and velocities are obtained. The pressure gradient and volume flow rate for different values of the biviscosity are also premeditated. The flow possessions for the biviscosity fluid resolute as a function of the cilia and metachronal wave velocity.
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Yu, Yanan, Kyosuke Shinohara, Huanming Xu, Zhenfeng Li, Tomoki Nishida, Hiroshi Hamada, Yuanqing Xu, et al. "The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization." Cellular Physiology and Biochemistry 51, no. 6 (2018): 2843–57. http://dx.doi.org/10.1159/000496038.
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Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.
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Flaherty, Justin, Zhe Feng, Zhangli Peng, Y. N. Young, and Andrew Resnick. "Primary cilia have a length-dependent persistence length." Biomechanics and Modeling in Mechanobiology 19, no. 2 (September 9, 2019): 445–60. http://dx.doi.org/10.1007/s10237-019-01220-7.
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Abstract The fluctuating position of an optically trapped cilium tip under untreated and Taxol-treated conditions was used to characterize mechanical properties of the cilium axoneme and its basal body by combining experimental, analytical, and computational tools. We provide, for the first time, evidence that the persistence length of a ciliary axoneme is length-dependent; longer cilia are stiffer than shorter cilia. We demonstrate that this apparent length dependence can be understood by a combination of modeling axonemal microtubules as anisotropic elastic shells and including actomyosin-driven stochastic basal body motion. Our results also demonstrate the possibility of using observable ciliary dynamics to probe interior cytoskeletal dynamics. It is hoped that our improved characterization of cilia will result in deeper understanding of the biological function of cellular flow sensing by this organelle.
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Sareh, Sina, Jonathan Rossiter, Andrew Conn, Knut Drescher, and Raymond E. Goldstein. "Swimming like algae: biomimetic soft artificial cilia." Journal of The Royal Society Interface 10, no. 78 (January 6, 2013): 20120666. http://dx.doi.org/10.1098/rsif.2012.0666.
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Cilia are used effectively in a wide variety of biological systems from fluid transport to thrust generation. Here, we present the design and implementation of artificial cilia, based on a biomimetic planar actuator using soft-smart materials. This actuator is modelled on the cilia movement of the alga Volvox , and represents the cilium as a piecewise constant-curvature robotic actuator that enables the subsequent direct translation of natural articulation into a multi-segment ionic polymer metal composite actuator. It is demonstrated how the combination of optimal segmentation pattern and biologically derived per-segment driving signals reproduce natural ciliary motion. The amenability of the artificial cilia to scaling is also demonstrated through the comparison of the Reynolds number achieved with that of natural cilia.
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Peabody, Jacelyn E., Ren-Jay Shei, Brent M. Bermingham, Scott E. Phillips, Brett Turner, Steven M. Rowe, and George M. Solomon. "Seeing cilia: imaging modalities for ciliary motion and clinical connections." American Journal of Physiology-Lung Cellular and Molecular Physiology 314, no. 6 (June 1, 2018): L909—L921. http://dx.doi.org/10.1152/ajplung.00556.2017.
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The respiratory tract is lined with multiciliated epithelial cells that function to move mucus and trapped particles via the mucociliary transport apparatus. Genetic and acquired ciliopathies result in diminished mucociliary clearance, contributing to disease pathogenesis. Recent innovations in imaging technology have advanced our understanding of ciliary motion in health and disease states. Application of imaging modalities including transmission electron microscopy, high-speed video microscopy, and micron-optical coherence tomography could improve diagnostics and be applied for precision medicine. In this review, we provide an overview of ciliary motion, imaging modalities, and ciliopathic diseases of the respiratory system including primary ciliary dyskinesia, cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis.
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Ito, Hiroaki, Toshihiro Omori, and Takuji Ishikawa. "Swimming mediated by ciliary beating: comparison with a squirmer model." Journal of Fluid Mechanics 874 (July 12, 2019): 774–96. http://dx.doi.org/10.1017/jfm.2019.490.
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The squirmer model of Lighthill and Blake has been widely used to analyse swimming ciliates. However, real ciliates are covered by hair-like organelles, called cilia; the differences between the squirmer model and real ciliates remain unclear. Here, we developed a ciliate model incorporating the distinct ciliary apparatus, and analysed motion using a boundary element–slender-body coupling method. This methodology allows us to accurately calculate hydrodynamic interactions between cilia and the cell body under free-swimming conditions. Results showed that an antiplectic metachronal wave was optimal in the swimming speed with various cell-body aspect ratios, which is consistent with former theoretical studies. Exploiting oblique wave propagation, we reproduced a helical trajectory, like Paramecium, although the cell body was spherical. We confirmed that the swimming velocity of model ciliates was well represented by the squirmer model. However, squirmer modelling outside the envelope failed to estimate the energy costs of swimming; over 90 % of energy was dissipated inside the ciliary envelope. The optimal swimming efficiency was given by the antiplectic wave; the value was 6.7 times larger than in-phase beating. Our findings provide a fundamental basis for modelling swimming micro-organisms.
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Kupferberg, Stephen B., John P. Bent, and Edward S. Porubsky. "The Evaluation of Ciliary Function: Electron versus Light Microscopy." American Journal of Rhinology 12, no. 3 (May 1998): 199–202. http://dx.doi.org/10.2500/105065898781390172.
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Diagnosing Primary Ciliary Dyskinesia can often be difficult. Physical findings suggest the disease, but definitive diagnosis should be made with a ciliary biopsy. Twenty biopsies were obtained from 16 patients and all underwent both light and electron microscopic examination. In 8/20 (40%) there was a discrepancy between the different imaging techniques. Therefore, light microscopy should be used to assess adequacy of biopsy and motion of the cilia along with electron microscopy to examine ultrastructure.
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Hoque, Mohammed, Eunice N. Kim, Danny Chen, Feng-Qian Li, and Ken-Ichi Takemaru. "Essential Roles of Efferent Duct Multicilia in Male Fertility." Cells 11, no. 3 (January 20, 2022): 341. http://dx.doi.org/10.3390/cells11030341.
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Cilia are microtubule-based hair-like organelles on the cell surface. Cilia have been implicated in various biological processes ranging from mechanosensation to fluid movement. Ciliary dysfunction leads to a plethora of human diseases, known as ciliopathies. Although non-motile primary cilia are ubiquitous, motile multicilia are found in restricted locations of the body, such as the respiratory tract, the oviduct, the efferent duct, and the brain ventricles. Multicilia beat in a whip-like motion to generate fluid flow over the apical surface of an epithelium. The concerted ciliary motion provides the driving force critical for clearing airway mucus and debris, transporting ova from the ovary to the uterus, maintaining sperm in suspension, and circulating cerebrospinal fluid in the brain. In the male reproductive tract, multiciliated cells (MCCs) were first described in the mid-1800s, but their importance in male fertility remained elusive until recently. MCCs exist in the efferent ducts, which are small, highly convoluted tubules that connect the testis to the epididymis and play an essential role in male fertility. In this review, we will introduce multiciliogenesis, discuss mouse models of male infertility with defective multicilia, and summarize our current knowledge on the biological function of multicilia in the male reproductive tract.
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Han, Jihun, and Charles S. Peskin. "Spontaneous oscillation and fluid–structure interaction of cilia." Proceedings of the National Academy of Sciences 115, no. 17 (April 9, 2018): 4417–22. http://dx.doi.org/10.1073/pnas.1712042115.
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The exact mechanism to orchestrate the action of hundreds of dynein motor proteins to generate wave-like ciliary beating remains puzzling and has fascinated many scientists. We present a 3D model of a cilium and the simulation of its beating in a fluid environment. The model cilium obeys a simple geometric constraint that arises naturally from the microscopic structure of a real cilium. This constraint allows us to determine the whole 3D structure at any instant in terms of the configuration of a single space curve. The tensions of active links, which model the dynein motor proteins, follow a postulated dynamical law, and together with the passive elasticity of microtubules, this dynamical law is responsible for the ciliary motions. In particular, our postulated tension dynamics lead to the instability of a symmetrical steady state, in which the cilium is straight and its active links are under equal tensions. The result of this instability is a stable, wave-like, limit cycle oscillation. We have also investigated the fluid–structure interaction of cilia using the immersed boundary (IB) method. In this setting, we see not only coordination within a single cilium but also, coordinated motion, in which multiple cilia in an array organize their beating to pump fluid, in particular by breaking phase synchronization.
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Ohmura, Takuya, Yukinori Nishigami, Atsushi Taniguchi, Shigenori Nonaka, Junichi Manabe, Takuji Ishikawa, and Masatoshi Ichikawa. "Simple mechanosense and response of cilia motion reveal the intrinsic habits of ciliates." Proceedings of the National Academy of Sciences 115, no. 13 (March 12, 2018): 3231–36. http://dx.doi.org/10.1073/pnas.1718294115.
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An important habit of ciliates, namely, their behavioral preference for walls, is revealed through experiments and hydrodynamic simulations. A simple mechanical response of individual ciliary beating (i.e., the beating is stalled by the cilium contacting a wall) can solely determine the sliding motion of the ciliate along the wall and result in a wall-preferring behavior. Considering ciliate ethology, this mechanosensing system is likely an advantage in the single cell’s ability to locate nutrition. In other words, ciliates can skillfully use both the sliding motion to feed on a surface and the traveling motion in bulk water to locate new surfaces according to the single “swimming” mission.
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Khaderi, S. N., J. M. J. den Toonder, and P. R. Onck. "Microfluidic propulsion by the metachronal beating of magnetic artificial cilia: a numerical analysis." Journal of Fluid Mechanics 688 (October 20, 2011): 44–65. http://dx.doi.org/10.1017/jfm.2011.355.
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AbstractIn this work we study the effect of metachronal waves on the flow created by magnetically driven plate-like artificial cilia in microchannels using numerical simulations. The simulations are performed using a coupled magneto-mechanical solid–fluid computational model that captures the physical interactions between the fluid flow, ciliary deformation and applied magnetic field. When a rotating magnetic field is applied to super-paramagnetic artificial cilia, they mimic the asymmetric motion of natural cilia, consisting of an effective and recovery stroke. When a phase difference is prescribed between neighbouring cilia, metachronal waves develop. Due to the discrete nature of the cilia, the metachronal waves change direction when the phase difference becomes sufficiently large, resulting in antiplectic as well as symplectic metachrony. We show that the fluid flow created by the artificial cilia is significantly enhanced in the presence of metachronal waves and that the fluid flow becomes unidirectional. Antiplectic metachrony is observed to lead to a considerable enhancement in flow compared to symplectic metachrony, when the cilia spacing is small. Obstruction of flow in the direction of the effective stroke for the case of symplectic metachrony was found to be the key mechanism that governs this effect.
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Shakib Arslan, Muhammad, Zaheer Abbas, and Muhammad Yousuf Rafiq. "Biological flow of thermally intense cilia generated motion of non-Newtonian fluid in a curved channel." Advances in Mechanical Engineering 15, no. 3 (March 2023): 168781322311571. http://dx.doi.org/10.1177/16878132231157179.
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The energy loss during the beating cilia phenomenon in the human stomach causing acidity in the blood flow under certain conditions has been a serious topic in the modern medical field. Therefore, the current study intends to exhibit a theoretical analysis of mixed convective transport of non-Newtonian Casson fluid observed by ciliary motion walls in the curved channel. The flow of constitutive equations is used to modify in curvilinear coordinates into a wave frame for two-dimensional flow due to the complication of the flow regime. The attributes of biological ciliary approximation are revealed through the control of viscous and inertial impacts utilizing the long-wavelength assumption and obtained the analytical closed form solutions for the normalized equations. The impacts of physical parameters on the velocity profile and heat flow phenomena are discussed. It is observed that the flow velocity, the momentum bolus and the trapped bolus are reduced in the cilia transport channel by enhancing the channel curvature. A validity of admirable comparison is also noticed with previously results.
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Paff, Tamara, Heymut Omran, Kim G. Nielsen, and Eric G. Haarman. "Current and Future Treatments in Primary Ciliary Dyskinesia." International Journal of Molecular Sciences 22, no. 18 (September 11, 2021): 9834. http://dx.doi.org/10.3390/ijms22189834.
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Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. In this review, we give a detailed overview of the clinical studies performed investigating PCD to date, including three trials and several case reports. In addition, we explore precision medicine approaches in PCD, including gene therapy, mRNA transcript and read-through therapy.
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Yang, T. Tony, Minh Nguyet Thi Tran, Weng Man Chong, Chia-En Huang, and Jung-Chi Liao. "Single-particle tracking localization microscopy reveals nonaxonemal dynamics of intraflagellar transport proteins at the base of mammalian primary cilia." Molecular Biology of the Cell 30, no. 7 (March 21, 2019): 828–37. http://dx.doi.org/10.1091/mbc.e18-10-0654.
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Primary cilia play a vital role in cellular sensing and signaling. An essential component of ciliogenesis is intraflagellar transport (IFT), which is involved in IFT protein recruitment, axonemal engagement of IFT protein complexes, and so on. The mechanistic understanding of these processes at the ciliary base was largely missing, because it is challenging to observe the motion of IFT proteins in this crowded region using conventional microscopy. Here, we report short-trajectory tracking of IFT proteins at the base of mammalian primary cilia by optimizing single-particle tracking photoactivated localization microscopy for IFT88-mEOS4b in live human retinal pigment epithelial cells. Intriguingly, we found that mobile IFT proteins “switched gears” multiple times from the distal appendages (DAPs) to the ciliary compartment (CC), moving slowly in the DAPs, relatively fast in the proximal transition zone (TZ), slowly again in the distal TZ, and then much faster in the CC. They could travel through the space between the DAPs and the axoneme without following DAP structures. We further revealed that BBS2 and IFT88 were highly populated at the distal TZ, a potential assembly site. Together, our live-cell single-particle tracking revealed region-dependent slowdown of IFT proteins at the ciliary base, shedding light on staged control of ciliary homeostasis.
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Patel-King, Ramila S., Miho Sakato-Antoku, Maya Yankova, and Stephen M. King. "WDR92 is required for axonemal dynein heavy chain stability in cytoplasm." Molecular Biology of the Cell 30, no. 15 (July 15, 2019): 1834–45. http://dx.doi.org/10.1091/mbc.e19-03-0139.
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WDR92 associates with a prefoldin-like cochaperone complex and known dynein assembly factors. WDR92 has been very highly conserved and has a phylogenetic signature consistent with it playing a role in motile ciliary assembly or activity. Knockdown of WDR92 expression in planaria resulted in ciliary loss, reduced beat frequency and dyskinetic motion of the remaining ventral cilia. We have now identified a Chlamydomonas wdr92 mutant that encodes a protein missing the last four WD repeats. The wdr92-1 mutant builds only ∼0.7-μm cilia lacking both inner and outer dynein arms, but with intact doublet microtubules and central pair. When cytoplasmic extracts prepared by freeze/thaw from a control strain were fractionated by gel filtration, outer arm dynein components were present in several distinct high molecular weight complexes. In contrast, wdr92-1 extracts almost completely lacked all three outer arm heavy chains, while the IFT dynein heavy chain was present in normal amounts. A wdr92-1 tpg1-2 double mutant builds ∼7-μm immotile flaccid cilia that completely lack dynein arms. These data indicate that WDR92 is a key assembly factor specifically required for the stability of axonemal dynein heavy chains in cytoplasm and suggest that cytoplasmic/IFT dynein heavy chains use a distinct folding pathway.
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Gueron, Shay, and Konstantin Levit-Gurevich. "Computation of the Internal Forces in Cilia: Application to Ciliary Motion, the Effects of Viscosity, and Cilia Interactions." Biophysical Journal 74, no. 4 (April 1998): 1658–76. http://dx.doi.org/10.1016/s0006-3495(98)77879-8.
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Farooq, A. A., and A. M. Siddiqui. "Mathematical model for the ciliary-induced transport of seminal liquids through the ductuli efferentes." International Journal of Biomathematics 10, no. 03 (February 20, 2017): 1750031. http://dx.doi.org/10.1142/s1793524517500310.
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This study describes the consequences of the ciliary motion on the transport of seminal liquid through the ductus efferentes of the male reproductive tract. By assuming the seminal liquid as a couple stress fluid, we have formulated a mathematical model for a two-dimensional flow through an axially symmetric tube whose inner surface is ciliated in the form of a metachronal wave. The governing system consists of nonlinear coupled partial differential equations which is reduced to a system of ordinary differential equations by utilizing the long wavelength approximation in an environment of the inertia free flow. Exact solutions for the velocity distribution, the pressure gradient and the stream function are obtained in terms of the couple stress parameters and the ciliary metachronism. Special attention is given to the pumping and the trapping characteristics due to the cilia motility. The study reveals that the ciliary pumping has to be more efficient to transport a couple stress fluid as compared to a Newtonian fluid. Moreover, the theoretical results for the couple stress fluid are found to be in good agreement with those reported by [T. J. Lardner and W. J. Shack, Cilia transport, Bull. Math. Biophys. 34 (1972) 325–335]. The analytical results are also displayed in graphical form.
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Kiyota, Kouki, Hironori Ueno, Keiko Numayama-Tsuruta, Tomofumi Haga, Yohsuke Imai, Takami Yamaguchi, and Takuji Ishikawa. "Fluctuation of cilia-generated flow on the surface of the tracheal lumen." American Journal of Physiology-Lung Cellular and Molecular Physiology 306, no. 2 (January 15, 2014): L144—L151. http://dx.doi.org/10.1152/ajplung.00117.2013.
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Although we inhale air that contains many harmful substances, including, for example, dust and viruses, these small particles are trapped on the surface of the tracheal lumen and transported towards the larynx by cilia-generated flow. The transport phenomena are affected not only by the time- and space-average flow field but also by the fluctuation of the flow. Because flow fluctuation has received little attention, we investigated it experimentally in mice. To understand the origin of flow fluctuation, we first measured the distribution of ciliated cells in the trachea and individual ciliary motions. We then measured the detailed flow field using a confocal micro-PTV system. Strong flow fluctuations were observed, caused by the unsteadiness of the ciliary beat and the spatial inhomogeneity of ciliated cells. The spreading of particles relative to the bulk motion became diffusive if the time scale was sufficiently larger than the beat period. Finally, we quantified the effects of flow fluctuation on bulk flow by evaluating the Peclet number of the system, which indicated that the directional transport was an order of magnitude larger than the isotropic diffusion. These results are important in understanding transport phenomena in the airways on a cellular scale.
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Salman, Huseyin Enes, Nathalie Jurisch-Yaksi, and Huseyin Cagatay Yalcin. "Computational Modeling of Motile Cilia-Driven Cerebrospinal Flow in the Brain Ventricles of Zebrafish Embryo." Bioengineering 9, no. 9 (August 28, 2022): 421. http://dx.doi.org/10.3390/bioengineering9090421.
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Motile cilia are hair-like microscopic structures which generate directional flow to provide fluid transport in various biological processes. Ciliary beating is one of the sources of cerebrospinal flow (CSF) in brain ventricles. In this study, we investigated how the tilt angle, quantity, and phase relationship of cilia affect CSF flow patterns in the brain ventricles of zebrafish embryos. For this purpose, two-dimensional computational fluid dynamics (CFD) simulations are performed to determine the flow fields generated by the motile cilia. The cilia are modeled as thin membranes with prescribed motions. The cilia motions were obtained from a two-day post-fertilization zebrafish embryo previously imaged via light sheet fluorescence microscopy. We observed that the cilium angle significantly alters the generated flow velocity and mass flow rates. As the cilium angle gets closer to the wall, higher flow velocities are observed. Phase difference between two adjacent beating cilia also affects the flow field as the cilia with no phase difference produce significantly lower mass flow rates. In conclusion, our simulations revealed that the most efficient method for cilia-driven fluid transport relies on the alignment of multiple cilia beating with a phase difference, which is also observed in vivo in the developing zebrafish brain.
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Akbar, Noreen Sher, and Adil Wahid Butt. "Heat transfer analysis of viscoelastic fluid flow due to metachronal wave of cilia." International Journal of Biomathematics 07, no. 06 (November 2014): 1450066. http://dx.doi.org/10.1142/s1793524514500661.
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This study describes ciliary motion on the transport of fluids in human body with heat transfer. The mathematical model of the flow of a Jeffrey fluid in a tube of finite length is considered due to metachronal wave of cilia motion. Flow equations have been modeled and simplified using similarity variables. Exact solutions of the formulated problem have been obtained for velocity, temperature and pressure gradient and graphs for velocity, pressure rise, pressure gradient and temperature profile have been plotted and studied for different values of specific physical parameters. Trapping phenomena and isotherms are presented at the end of the paper.
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Sher Akbar, Noreen. "Biomathematical analysis of carbon nanotubes due to ciliary motion." International Journal of Biomathematics 08, no. 02 (February 25, 2015): 1550023. http://dx.doi.org/10.1142/s1793524515500230.
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In this paper, the consequences of cilia motion are reflected by the CNTs nanoparticles. The problem is expressed in a symmetric channel with ciliated walls. Exact solutions of the governing flow problem are obtained for pressure gradient, temperature and velocities of the fluid. Streamlines for the velocity profile are plotted to discuss the trapping phenomenon.
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Cui, Zhiwei, Ye Wang, and Jaap M. J. den Toonder. "Metachronal Motion of Biological and Artificial Cilia." Biomimetics 9, no. 4 (March 27, 2024): 198. http://dx.doi.org/10.3390/biomimetics9040198.
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Cilia are slender, hair-like cell protrusions that are present ubiquitously in the natural world. They perform essential functions, such as generating fluid flow, propulsion, and feeding, in organisms ranging from protozoa to the human body. The coordinated beating of cilia, which results in wavelike motions known as metachrony, has fascinated researchers for decades for its role in functions such as flow generation and mucus transport. Inspired by nature, researchers have explored diverse materials for the fabrication of artificial cilia and developed several methods to mimic the metachronal motion observed in their biological counterparts. In this review, we will introduce the different types of metachronal motion generated by both biological and artificial cilia, the latter including pneumatically, photonically, electrically, and magnetically driven artificial cilia. Furthermore, we review the possible applications of metachronal motion by artificial cilia, focusing on flow generation, transport of mucus, particles, and droplets, and microrobotic locomotion. The overall aim of this review is to offer a comprehensive overview of the metachronal motions exhibited by diverse artificial cilia and the corresponding practical implementations. Additionally, we identify the potential future directions within this field. These insights present an exciting opportunity for further advancements in this domain.
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Pang, Chuan, Fengwei An, Shiming Yang, Ning Yu, Daishi Chen, and Lei Chen. "In vivo and in vitro observation of nasal ciliary motion in a guinea pig model." Experimental Biology and Medicine 245, no. 12 (May 20, 2020): 1039–48. http://dx.doi.org/10.1177/1535370220926443.
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In vitro airway specimens are widely used to evaluate airway ciliary function. However, the function of in vitro ciliated cells may be far different from their actual in vivo physiological conditions. Due to the lack of a valid technique, direct images of in vivo airway ciliary motion have never been captured and analyzed before. This study aims to examine nasal ciliary motion in living guinea pigs with comparison to in vitro observation. Nasal septum mucosa was exposed in anaesthetized guinea pigs and directly examined using a digital microscopy system. The study included three parts: (1) measurement of ciliary beat frequency (CBF) of nasal mucosa at room temperature in living guinea pigs and immediately after death, and in dissected mucosa specimens/cells for comparison; (2) monitoring of nasal ciliary motion, CBF, and ciliary beat distance (CBD) over 12 h in both living guinea pigs and dissected mucosa specimens/cells; and (3) measurement of ciliary motion changes in responses to temperature variations. Compared with when the animal was alive, the CBF after death and in dissected mucosa specimens/cells was lower by about 20% ( P < 0.05). CBF and CBD variation in living guinea pigs was within 10% over time. The slope of CBF/temperature profile was 0.18 ± 0.01 Hz/°C in living guinea pigs, 0.51 ± 0.02 Hz/°C for dissected mucosa specimens, and 0.48 ± 0.03 Hz/°C for isolated ciliary cells. The technique described in this study makes it feasible to study ciliary motion in living animals using the digital microscope system. Ciliary function changes immediately after death. Ciliary motion in a living animal is more stable over time and has a different response to temperature change as compared with in vitro observation results. Impact statement Cilia play an important role in the airway defense mechanism. So far, studies on ciliary function have mainly been based on in vitro methods. Images of in vivo ciliary motion are very difficult to capture. In this study, we describe a novel approach to observe and analyze nasal ciliary motion in living animals with comparison to in vitro observation. Such images of ciliary motion from living animals have not been reported to date. The result of the study indicates that in vivo ciliary physiological function differs from ex vivo and in vitro conditions in many ways, such as the stability over time and response to temperature variation. This is a good foundation for further in vivo analysis of airway ciliary physiological function in animals as well as humans.
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Ramachandran, Saravana, Kuppalapalle Vajravelu, K. V. Prasad, and S. Sreenadh. "Peristaltic-Ciliary Flow of A Casson Fluid through An Inclined Tube." Communication in Biomathematical Sciences 4, no. 1 (May 7, 2021): 23–38. http://dx.doi.org/10.5614/cbms.2021.4.1.3.
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The paper is concerned with the peristaltic-ciliary transport of a viscoplastic fluid (Casson fluid) through an inclined cylindrical tube. The peristalsis-cilia induced motion is analysed in the moving frame of reference under the lubrication approximations. Solutions to the flow characteristics petering to yielded and unyielded regions are obtained. The effects of various physical parameters on the axial velocity, the pumping characteristics, the pressure rise, and the frictional force over one wavelength, along with the trapping phenomenon are presented through graphs. Further, the peristaltic flow and peristaltic-ciliary flow results are compared. It is noticed that the axial velocity and the size of trapping bolus in the unplug flow region decrease with an increase in the yield stress. In addition, the axial velocity and the axial pressure gradient in the peristaltic-ciliary pumping are higher than those in the peristaltic pumping.
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Morgan, Darrell D., and Anthony G. Moss. "The Effects of Cigarette Smoke on Porcine Airway Epithelium." Microscopy and Microanalysis 4, S2 (July 1998): 1076–77. http://dx.doi.org/10.1017/s1431927600025502.
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Cephalad pulmonary mucociliary clearance driven by cilia of the ciliated airway epithelium provides probably the most important line of defense against inhaled toxins and particulate material for organs of the thoracic cavity. We demonstrate the reorganization of the cytoskeleton and the endoplasmic reticulum of airway epithelial cells upon cigarette smoke inhalation by employing DIC, LSCM, TEM and widefield fluorescence microscopy and have correlated this reorganization to changes in ciliary beat frequency (CBF) via FFT analysis. Neonatal pigs were used to provided healthy tracheal epithelial tissue. Exposure to cigarette smoke causes rapid ultrastructural changes including: ciliary distortion and detachment, ciliary abscission and severe alteration in endoplasmic reticulum structure suggesting profound disruption of essential membrane-cytoskeletal linkages.To examine changes in CBF we describe a simple approach, using a laser scanning confocal microscope (LSCM) and an analog-to-digital computer converter/analyzer for the acquisition of data from biological systems that undergo rapid periodic movement, such as ciliary motion.
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Wyatt, Todd A., Mary A. Forgèt, Jennifer M. Adams, and Joseph H. Sisson. "Both cAMP and cGMP are required for maximal ciliary beat stimulation in a cell-free model of bovine ciliary axonemes." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 3 (March 2005): L546—L551. http://dx.doi.org/10.1152/ajplung.00107.2004.
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Previously, we have shown that the ATPase-dependent motion of cilia in bovine bronchial epithelial cells (BBEC) can be regulated through the cyclic nucleotides, cAMP via the cAMP-dependent protein kinase (PKA) and cGMP via the cGMP-dependent protein kinase (PKG). Both cyclic nucleotides cause an increase in cilia beat frequency (CBF). We hypothesized that cAMP and cGMP may act directly at the level of the ciliary axoneme in BBEC. To examine this, we employed a novel cell-free system utilizing detergent-extracted axonemes. Axoneme movement was whole-field analyzed digitally with the Sisson-Ammons video analysis system. A suspension of extracted axonemes remains motionless until the addition of 1 mM ATP that establishes a baseline CBF similar to that seen when analyzing intact ciliated BBEC. Adding 10 μM cAMP or 10 μM cGMP increases CBF beyond the established ATP baseline. However, the cyclic nucleotides did not stimulate CBF in the absence of ATP. Therefore, the combination of cAMP and cGMP augments ATP-driven CBF increases at the level of isolated axoneme.
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Ferguson, Jonathan L., Thomas V. McCaffrey, Eugene B. Kern, and William J. Martin. "The Effects of Sinus Bacteria on Human Ciliated Nasal Epithelium in Vitro." Otolaryngology–Head and Neck Surgery 98, no. 4 (April 1988): 299–304. http://dx.doi.org/10.1177/019459988809800405.
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The mechanisms by which bacteria colonize and damage ciliated epithelium are important in understanding the pathophysiology of rhinitis, sinusitis, and otitis. Bacteria that have the ability to impair mucociliary clearance would be at an advantage in establishing infection of ciliated surfaces. This study investigates the effect of Hemophilus Influenzae, Streptococcus pneumoniae, Brahmanella catarralis, and Staphylococcus epidermidis on the ciliary activity of normal ciliated nasal epithelium in human beings. Ciliary activity of the nasal epithelium in the presence of each pathogen was assessed for more than 240 minutes with a photometric method of ciliary beat frequency (CBF) measurement. H. influenzae exerted significant effects on ciliary activity, with a 46% decrease in the CBF by 4 hours (with bacteria-containing broth) and a 32% decrease with bacteria-free filtrate. S. epidermidis decreased CBF by 44% with the bacterial broth. A sterile cell-free filtrate had no significant effect. S. pneumoniae and B. catarralis had no significant effect on CBF within a 240-minute period. H. influenzae and S. epidermidis disrupted normal synchronous ciliary motion, causing adjacent cilia to beat at different rates.
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WU, Junlin, Jiaqi Yin, Zixiang Xu, Yingli Liu, Huanyong Qin, and Xin Sheng. "The function of ciliopathy protein FOP on cilia and cortical microtubule cytoskeleton in Euplotes amieti." Acta Protozoologica 62 (2023): 45–56. http://dx.doi.org/10.4467/16890027ap.23.005.18868.
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FOP is a centriole satellite protein involved in ciliogenesis. Although centriole satellites are involved in centrosome and ciliumrelated protein trafficking, their functions related to ciliary assembly and maintenance of ciliary microtubule stability remain unclear. In this study, the function of the FOP gene in Euplotes amieti was investigated by interfering with its expression using RNAi. As a result, expression levels of the ciliary assembly-related proteins BBS8 and IFT88 were down-regulated. Swimming speeds also decreased and the Euplotes were only able to spin in circles, which suggested that the FOP protein is an important protein involved in ciliary motion. Further observations of Euplotes amieti microstructure and ultrastructure via immunofluorescence and transmission electron microscopy revealed that FOP not only participated in the formation of the ventral ciliary basal body but also played an important role in the maintenance of cortical microtubules, which is fundamental for the morphological structure of Euplotes amieti.
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Stokes, M. "Larval locomotion of the lancelet." Journal of Experimental Biology 200, no. 11 (January 1, 1997): 1661–80. http://dx.doi.org/10.1242/jeb.200.11.1661.
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The ontogeny of locomotion in the Florida lancelet (Branchiostoma floridae) is described for the early developmental stages through to metamorphosis. Recently hatched larvae swam at speeds up to 1 mm s-1 using their epidermal cilia; this speed decreased to approximately 0.2 mm s-1 by 60 h after fertilization. Changes in cilia-powered fluid flow could be related to changes in the distribution and density of the epidermal cilia during development. Cilia-powered hovering was the dominant behaviour until metamorphosis. The amount of energy expended by ciliating larvae ranged from 10(-9) to 10(-11) W depending upon the age of the larvae and the model used for estimating the power output. The majority of the energy expended was in the ciliary sublayer next to the body. The first muscular movements were seen in larvae 16 h old. These simple flexions increased in complexity during the first 72 h until a complete undulatory (approximately sinusoidal) wave was propagated down the body in the adult manner. The frequency of undulatory beating increased to approximately 10 Hz during the first 48 h, and the larval head showed a large degree of yaw. Lancelet larvae were also capable of high-speed undulations 5­10 times faster than regular swimming motions. In contrast to ciliating larvae, the energy expended during undulation was at least an order of magnitude greater (10(-8) to 10(-6) W) and radiated beyond the ciliary sublayer.
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UENO, Hironori, Takuji ISHIKAWA, Khanh Huy BUI, Kohsuke GONDA, Takashi ISHIKAWA, and Takami YAMAGUCHI. "7G13 Analysis of ciliary motion and the axonemal structure in the mouse respiratory cilia." Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME 2012.24 (2012): _7G13–1_—_7G13–2_. http://dx.doi.org/10.1299/jsmebio.2012.24._7g13-1_.
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Roth, K. E., C. L. Rieder, and S. S. Bowser. "Flexible-substratum technique for viewing cells from the side: some in vivo properties of primary (9+0) cilia in cultured kidney epithelia." Journal of Cell Science 89, no. 4 (April 1, 1988): 457–66. http://dx.doi.org/10.1242/jcs.89.4.457.
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Cells cultured on thin plastic (e.g. Formvar, Teflon, polycarbonate) membranes can be clearly imaged from the side in vivo by video microscopy. We have used this flexible-substratum technique to examine the behaviour and properties of primary cilia in confluent cultures of the kidney epithelial cell lines PtK1, PtK2, LLC-PK1, MDCK and BSC-40. In these cells primary cilia appear as rigid rods, up to 55 micron long, which project at various angles from the dorsal cell surface. The length distribution of primary cilia in confluent cultures is a distinct characteristic of each established kidney cell line examined, with LLC-PK1 exhibiting three distinct length populations. Primary cilia of kidney cell lines bend passively in response to flow but do not display propagated bending or vortical motions. Up to 26% of the cilia in the cell types examined possess one or more conspicuous swellings along the ciliary shaft. Treatment with 0.05% trypsin, which is sufficient to cause cell rounding, does not induce the resorption or shedding of the cilium. These direct observations demonstrate that kidney epithelial-cell primary cilia are non-motile and longer than previously thought, and suggest that their length represents a phenotypic marker for each cell line.
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Smith, D. J., E. A. Gaffney, and J. R. Blake. "Mathematical modelling of cilia-driven transport of biological fluids." Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 465, no. 2108 (June 2, 2009): 2417–39. http://dx.doi.org/10.1098/rspa.2009.0018.
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Cilia-driven flow occurs in the airway surface liquid, in the female and male reproductive tracts and enables symmetry-breaking in the embryonic node. Viscoelastic rheology is found in healthy states in some systems, whereas in others may characterise disease, motivating the development of mathematical models that take this effect into account. We derive the fundamental solution for linear viscoelastic flow, which is subsequently used as a basis for slender-body theory. Our numerical algorithm allows efficient computation of three-dimensional time-dependent flow, bending moments, power and particle transport. We apply the model to the large-amplitude motion of a single cilium in a linear Maxwell liquid. A relatively short relaxation time of just 0.032 times the beat period significantly reduces forces, bending moments, power and particle transport, the last variable exhibiting exponential decay with relaxation time. A test particle is propelled approximately one-fifth as quickly along the direction of cilia beating for scaled relaxation time 0.032 as in the Newtonian case, and mean volume flow is abolished, emphasizing the sensitivity of cilia function to fluid rheology. These results may have implications for flow in the airways, where the transition from Newtonian to viscoelastic rheology in the peri-ciliary fluid may reduce clearance.
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Siddiqui, A. M., A. A. Farooq, and M. A. Rana. "An investigation of non-Newtonian fluid flow due to metachronal beating of cilia in a tube." International Journal of Biomathematics 08, no. 02 (February 25, 2015): 1550016. http://dx.doi.org/10.1142/s1793524515500163.
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The aim of this study is to explain theoretically the role of ciliary motion on the transport of epididymal fluid through the ductus efferentes of the male reproductive track. For this purpose, a mathematical model has been developed for the flow of a non-Newtonian fluid in an axisymmetric tube due to metachronal wave of cilia motion for the more realistic consequences. Carreau viscous fluid model is considered to see the rheological effects on the pumping characteristics of the flow. Regular perturbation method has been employed to obtain the analytical expressions for the stream function, the velocity field and a relation between the pressure difference and the volume flow rate. It is found that the volume flow rate is influenced significantly by Weissenberg number We and the cilia length parameter ε. The computational results are presented graphically to see the effects of various physical parameters. Finally, the analysis is applied and compared with the observed value of the flow rate of spermatic fluid in the ductus efferentes of the male reproductive track. The volume flow rate is reported closed to the estimated value 6 × 10-3 ml/h in the human ductus efferentes when We = 0.5 and ε is near by 0.25.
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Umlauf, Benjamin. "DDEL-13. CILIA INHIBITORS SYNERGIZE WITH TEMOZOLOMIDE TO DRAMATICALLY IMPROVE SURVIVAL IN ORTHOTOPIC MURINE MODELS OF GLIOBLASTOMA." Neuro-Oncology 25, Supplement_5 (November 1, 2023): v104. http://dx.doi.org/10.1093/neuonc/noad179.0392.
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Abstract Patients with malignant brain tumors such as glioblastoma face a poor prognosis with a median survival of less than two years. Recent glymphatic studies demonstrate the interconnectivity between the fluid in the brain parenchymal and ventricular spaces. We reasoned enhancing the accumulation of a drug in the cerebral spinal fluid (CSF) of the ventricular space will also enhance the accumulation of the drug in the parenchyma where a GBM resides. To improve drug accumulation in the CSF, we modulated the motility of ependymal cell cilia. Ependymal cells coat the ventricles and display motile cilia that mechanically propel CSF through the ventricular space. Impairing ciliary motion could slow down CSF turnover without affecting the overall amount of CSF in the brain and central nervous system. To test these hypotheses, we identified FDA-approved therapeutics that are known to impair airway cilia as a “side effect.” Seven candidate drugs were administered into the ventricle of mice bearing orthotopic GBM in combination with systemic temozolomide. Five of the seven cilia-inhibiting drugs significantly improved overall survival when combined with temozolomide compared to controls. The lead candidate, lidocaine, demonstrated a synergistic relationship with temozolomide, and 100% of animals treated with the combination survived to the study endpoint tumor free. We demonstrate lidocaine can impair cilia motility in vitro and in vivo. Combining intraventricular lidocaine with temozolomide is well tolerated and results in a 2.8-fold increase in brain temozolomide concentration per dose compared to controls. Finally, we validate these data in two human PDX orthotopic xenograft GBM murine models, including an un-methylated MGMT GBM that became sensitive to temozolomide with the combination treatment. These studies offer a new concept for treating malignant brain tumors and potentially a scheme to improve the treatment of additional encephalopathies in the future.
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Satir, P. "Mechanism of Ciliary Movement - What's New?" Physiology 4, no. 4 (August 1, 1989): 153–57. http://dx.doi.org/10.1152/physiologyonline.1989.4.4.153.
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The basic structure of cilia and flagella is highly conserved in eukaryotes from protozoa to humans, but the motions they perform may be strikingly different. Combined electron microscopic and biochemical studies have led to a unifying hypothesis about how movement is generated that may explain the different behaviors.
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Blanchon, Sylvain, Marie Legendre, Mathieu Bottier, Aline Tamalet, Guy Montantin, Nathalie Collot, Catherine Faucon, et al. "Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia." Journal of Medical Genetics 57, no. 4 (November 26, 2019): 237–44. http://dx.doi.org/10.1136/jmedgenet-2019-106424.
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BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.
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Sisson, J. H., D. J. Tuma, and S. I. Rennard. "Acetaldehyde-mediated cilia dysfunction in bovine bronchial epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 260, no. 2 (February 1, 1991): L29—L36. http://dx.doi.org/10.1152/ajplung.1991.260.2.l29.
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Acetaldehyde, which is present in significant concentrations in cigarette smoke and is elevated during alcohol ingestion, has been demonstrated to impair mucociliary clearance of the lung. Acetaldehyde is also known to impair protein function through the formation of acetaldehyde-protein adducts. We hypothesized that acetaldehyde impairs bronchial epithelial cilia motion by inhibiting cilia dynein adenosinetriphosphatase (ATPase) activity through the formation of acetaldehyde adducts with cilia proteins. Acetaldehyde induced concentration- and time-dependent slowing of cilia beating and cilia-derived dynein ATPase activity in primary cultures and isolated axonemes of bovine airway epithelial cells. Cilia slowing and ATPase inhibitory effects were also observed with related aldehydes but not with ethanol. Acetaldehyde binding, assessed by gel electrophoresis using [14C] acetaldehyde, was demonstrated to occur with the dynein heavy chains and with tubulin and closely paralleled ATPase inhibition. We conclude that acetaldehyde directly impairs bronchial cilia function causing slowing of cilia beating, inhibits cilia dynein ATPase activity, and binds to cilia proteins critical for motion including dynein and tubulin. These data suggest that acetaldehyde-induced cilia dysfunction may be related to direct cilia ATPase inactivation and adduct formation with cilia dynein and tubulin. This may be an important mechanism by which airway host defenses are impaired in clinical settings where acetaldehyde exposure occurs, e.g., with cigarette smoking and alcohol ingestion.
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Masuda, Tsukuru, Aya Mizutani Akimoto, Kenichi Nagase, Teruo Okano, and Ryo Yoshida. "Artificial cilia as autonomous nanoactuators: Design of a gradient self-oscillating polymer brush with controlled unidirectional motion." Science Advances 2, no. 8 (August 2016): e1600902. http://dx.doi.org/10.1126/sciadv.1600902.
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A gradient self-oscillating polymer brush surface with ordered, autonomous, and unidirectional ciliary motion has been designed. The self-oscillating polymer is a random copolymer composed of N-isopropylacrylamide and ruthenium tris(2,2′-bipyridine) [Ru(bpy)3], which acts as a catalyst for an oscillating chemical reaction, the Belousov-Zhabotinsky reaction. The target polymer brush surface was designed to have a thickness gradient by using sacrificial-anode atom transfer radical polymerization. The gradient structure of the polymer brush was confirmed by x-ray photoelectron spectroscopy, atomic force microscopy, and ultraviolet-visible spectroscopy. These analyses revealed that the thickness of the polymer brush was in the range of several tens of nanometers, and the amount of Ru(bpy)3 increased as the thickness increased. The gradient polymer brush induced a unidirectional propagation of the chemical wave from the region with small Ru(bpy)3 amounts to the region with large Ru(bpy)3 amounts. This spatiotemporal control of the ciliary motion would be useful in potential applications to functional surface such as autonomous mass transport systems.
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Riaz, Arshad, Elena Bobescu, Katta Ramesh, and Rahmat Ellahi. "Entropy Analysis for Cilia-Generated Motion of Cu-Blood Flow of Nanofluid in an Annulus." Symmetry 13, no. 12 (December 8, 2021): 2358. http://dx.doi.org/10.3390/sym13122358.
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In this study, a novel model of entropy generation effects measured in the Cu-blood flow of a nanofluid under the effect of ciliary-oriented motion is proposed. The effects of viscous dissipation are also taken into account. The physical model was composed with the incorporation of a low Reynolds number and long-wavelength phenomena. The exact solutions for the axial velocity, temperature and pressure gradient distribution were achieved successfully. Key findings are presented through a strategy of plotting the significant factors affecting the physical quantities of the stream. It was found that the heat absorption parameter and Brownian motion accounted for the large thermal transfer rate, while the effect of entropy was minimal compared to these factors in the center of the flow but increased on the walls in the case of Cu-blood flow. It can also be added that a more intense flow gave rise to the entropy effects. This study may be helpful in medical science as cilia play vital roles, which include cell migration and external fluid transport, in human tissues and some key organs. Moreover, the considered annulus-shaped geometry gives vital readings that are used in medical equipment such as endoscopes.
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KANEKO, Toshiyasu, Kazuki WATANABE, Kenji NAGAOKA, and Kazuya YOSHIDA. "Motion Analysis of Ciliary Micro-Hopping Locomotion for an Asteroid Exploration Robot with Design Parameters of Cilia." Proceedings of JSME annual Conference on Robotics and Mechatronics (Robomec) 2016 (2016): 2A2–17a1. http://dx.doi.org/10.1299/jsmermd.2016.2a2-17a1.
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Hanasoge, Srinivas, Peter J. Hesketh, and Alexander Alexeev. "Metachronal motion of artificial magnetic cilia." Soft Matter 14, no. 19 (2018): 3689–93. http://dx.doi.org/10.1039/c8sm00549d.
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Ide, Takahiro, Wang Kyaw Twan, Hao Lu, Yayoi Ikawa, Lin-Xenia Lim, Nicole Henninger, Hiromi Nishimura, et al. "CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components." PLOS Genetics 16, no. 12 (December 21, 2020): e1009232. http://dx.doi.org/10.1371/journal.pgen.1009232.
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Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.
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MAXEY, MARTIN R. "Biomimetics and cilia propulsion." Journal of Fluid Mechanics 678 (June 17, 2011): 1–4. http://dx.doi.org/10.1017/jfm.2011.145.
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Many swimming microorganisms are able to propel themselves by the organized beating motion of numerous short flagella or cilia attached to their body surface. For their small size and the inherently viscous nature of the motion, this mechanism is very effective and they can swim several body lengths per second. The quest has been to see if artificial cilia may be developed and if the strategy of cilia propulsion can be used in microfluidic devices to transport fluids in a localized and controllable manner. Babataheri et al. (J. Fluid Mech., this issue, vol. 678, 2011, pp. 5–13) explore the response of chains of small paramagnetic beads that are elastically bonded together to form artificial cilia. The chain or fleximag is tethered to the surface and driven by external magnetic fields, responding also to both fluid and elastic forces. A key observation from their experiments and model is that for a simple planar-forcing strategy there is a hidden symmetry that limits the net transport of fluid.
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Man, Yi, Feng Ling, and Eva Kanso. "Cilia oscillations." Philosophical Transactions of the Royal Society B: Biological Sciences 375, no. 1792 (December 30, 2019): 20190157. http://dx.doi.org/10.1098/rstb.2019.0157.
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Cilia, or eukaryotic flagella, are microscopic active filaments expressed on the surface of many eukaryotic cells, from single-celled protozoa to mammalian epithelial surfaces. Cilia are characterized by a highly conserved and intricate internal structure in which molecular motors exert forces on microtubule doublets causing cilia oscillations. The spatial and temporal regulations of this molecular machinery are not well understood. Several theories suggest that geometric feedback control from cilium deformations to molecular activity is needed. Here, we implement a recent sliding control model, where the unbinding of molecular motors is dictated by the sliding motion between microtubule doublets. We investigate the waveforms exhibited by the model cilium, as well as the associated molecular motor dynamics, for hinged and clamped boundary conditions. Hinged filaments exhibit base-to-tip oscillations while clamped filaments exhibit both base-to-tip and tip-to-base oscillations. We report the change in oscillation frequencies and amplitudes as a function of motor activity and sperm number, and we discuss the validity of these results in the context of experimental observations of cilia behaviour. This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
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Hanasoge, Srinivas, Matthew Ballard, Peter J. Hesketh, and Alexander Alexeev. "Asymmetric motion of magnetically actuated artificial cilia." Lab on a Chip 17, no. 18 (2017): 3138–45. http://dx.doi.org/10.1039/c7lc00556c.
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Nakamura, S., and S. L. Tamm. "Calcium control of ciliary reversal in ionophore-treated and ATP-reactivated comb plates of ctenophores." Journal of Cell Biology 100, no. 5 (May 1, 1985): 1447–54. http://dx.doi.org/10.1083/jcb.100.5.1447.
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Previous work showed that ctenophore larvae swim backwards in high-KCl seawater, due to a 180 degrees reversal in the direction of effective stroke of their ciliary comb plates (Tamm, S. L., and S. Tamm, 1981, J. Cell Biol., 89: 495-509). Ion substitution and blocking experiments indicated that this response is Ca2+ dependent, but comb plate cells are innervated and presumably under nervous control. To determine whether Ca2+ is directly involved in activating the ciliary reversal mechanism and/or is required for synaptic triggering of the response, we (a) determined the effects of ionophore A23187 and Ca2+ on the beat direction of isolated nerve-free comb plates dissociated from larvae by hypotonic, divalent cation-free medium, and (b) used permeabilized ATP-reactivated models of comb plates to test motile responses to known concentrations of free Ca2+. We found that 5 microM A23187 and 10 mM Ca2+ induced dissociated comb plate cells to beat in the reverse direction and to swim counterclockwise in circular paths instead of in the normal clockwise direction. Detergent/glycerol-extracted comb plates beat actively in the presence of ATP, and reactivation was reversibly inhibited by micromolar concentrations of vanadate. Free Ca2+ concentrations greater than 10(-6)M caused reversal in direction of the effective stroke but no significant increase in beat frequency. These results show that ciliary reversal in ctenophores, like that in protozoa, is activated by an increase in intracellular free Ca2+ ions. This allows the unique experimental advantages of ctenophore comb plate cilia to be used for future studies on the site and mechanism of action of Ca2+ in the regulation of ciliary motion.